Origin of histiocyte-like cells and multinucleated giant cells in malignant fibrous histiocytoma: Neoplastic or reactive?

The origin of histiocyte-like cells in malignant fibrous histiocytoma (MFH) remains controversial. To determine whether histiocyte-like cells and mult inucleated giant cells show reactive or neoplastic proliferation, we transp lanted human storiform-pleomorphic MFH to nude mice and investigated the or igin of histiocyte-like cells using the DNA in situ hybridization (ISH) sys tem. In addition, we analyzed the mRNA expression of mouse c-fms and human colony stimulating factor-1 (CSF-I); immunohistochemical expression of mark ers detectable in,cells of monocyte/macrophage lineage. The DNA ISH reveale d neoplastic proliferation of fibroblastic cells and bizarre multinucleated giant cells of human origin. Monocyte/macrophage lineage cells were seen i n parental tumors, whereas they did not participate in neoplastic prolifera tion in transplanted tumors, The parental tumors expressed human CSF-1 mRNA and the histiocyte-like cells in transplanted tumors expressed 'mouse' c-f ms mRNA, These results suggest that MFH induce infiltration of monocyte/mac rophage and CSF-1 is one of the mediators involved in this phenomenon, beca use the human CSF-1 can act as a ligand to the mouse c-fms. Histiocyte-like cells in MFH should be considered as a reactive monocyte/macrophage lineag e rather than as an element of neoplasm.